Activity plays an important role in guiding the normal development of many areas in the central nervous system (CNS), and the retina is no exception. Interfering with normal sensory input at young ages has profound effects on the development of nervous tissue and can lead to permanent deficits in function. Raising rodents in the dark ("dark rearing") alters responses recorded in the output neurons of the retina, the retinal ganglion cells (RGCs). In order to identify how activity can guide maturation of CNS circuitry, the specific aims of this proposal seek to determine the alterations in retinal circuitry leading to these known changes in retinal output resulting from light-deprivation during development. The RGCs receive their input from bipolar cells, which release glutamate in response to photoreceptor activity. Inhibitory amacrine cells are important for proper control of this bipolar input to RGCs. Using whole- cell patch clamp techniques, the development of amacrine cell inputs to bipolar cells will be examined in the retinas of both normally reared and dark reared animals by recording spontaneous events and by evoking responses from reciprocal synapses made between bipolar terminals and amacrine dendrites. The ability of bipolar cells from different rearing conditions to release glutamate will also be studied by recording evoked responses in RGCs and by measuring calcium entry into isolated bipolar cell terminals, using calcium indicator dyes and fluorescent imaging of acutely isolated bipolar cells in culture. The goal is to determine whether these bipolar cell inputs and/or bipolar cell glutamate release properties are altered by activity deprivation during early development. These properties critically affect RGC output.